Novel compounds of amino sulfonyl derivatives
First Claim
Patent Images
1. A compound of formula (I):
- wherein;
R1 is 2-pyridinyl which is fused or substituted with 1-3 R6′
groups, with at least one R6 group being at the 6′
position of the pyridinyl;
b is 2;
R2 and R3 are taken together with the nitrogen atom to which they are attached to form a (4 to
11)-membered heterocyclyl, and the (4 to
11)-membered heterocyclyl may optionally be substituted by 1 to 3 R6 groups;
the carbon atoms of R1, R2, and R3 may each be optionally substituted by 1 to 3 R6 groups;
each R6 group is independently selected from the group consisting of halo, cyano, nitro, —
CF3, —
CHF2, —
CH2F, trifluoromethoxy, azido, hydroxy, (C1-C6)alkoxy, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, —
(CR7R8)v(C6-C12 aryl), —
(CR7R8)v(4 to
11)-membered heterocyclyl, —
(C═
O)—
R9, —
(C═
O)—
O—
R9, —
O—
(C═
O)—
R9, —
R9—
(C=O)—
O—
R10, —
(CR9R10)q(C═
O)(CR11R12)v(C6-C12)aryl, —
(CR9R10)q(C═
O)(CR11R12)v(4 to
11)-membered heterocyclyl, —
O—
(C═
O)—
NR13R14, —
NR13(C═
O)—
R14, —
(C═
O)—
NR13R14, —
R13—
(C═
O)—
NR14R15, —
NR13R14, —
NR13OR14, —
S(O)kNR13R14, —
S(O)j(C1-C6)alkyl, —
O—
SO2—
R15, —
NR15—
S(O)k—
R16, —
(CR17R18)qS(O)j(CR19R20)v(C6-C12)aryl, —
(CR17R18)qS(O)j(CR19R20)v(4 to
11)-membered heterocyclyl, —
(CR17R18)vO(CR19R20)q(C6-C12)aryl, and —
(CR17R18)vO(CR19R20)q(4 to
11)-membered heterocyclyl, -k is selected from 1 and 2;
j is selected from the group consisting of 0, 1, and 2;
t, u, p, q, and v are each independently selected from the group consisting of 0, 1, 2, 3, 4, and 5;
any 1 or 2 carbon atoms of any foregoing (4 to
11)-membered heterocyclyl groups may be optionally substituted with an oxo (═
O);
any (C1-C6)alkyl, any (C6-C12)aryl, and any (4 to
11)-membered heterocyclyl of the foregoing R6 groups may be optionally substituted with 1 to 3 substituents independently selected from the group consisting of halo, cyano, nitro, —
CF3, —
CFH2, —
CF2H, trifluoromethoxy, azido, —
OR21, —
(C═
O)—
R21, —
(C═
O)—
O—
R21, —
O—
(C═
O)—
R21, —
NR21(C═
O)—
R22, —
(C═
O)—
NR21R22, —
NR21R22, —
NR21OR22, (C1-C6)alkyl, (C2-C8)alkenyl, (C2-C6)alkynyl, —
(CR21R22)u(C6-C12)aryl, and —
(CR21R22)u(4 to
11)-membered heterocyclyl;
each R7, R8, R9, R10, R11, R12, R13, R14, R15, R16, R17, R18, R19, R20, R21, and R22 group is independently selected from the group consisting of H, (C1-C6)alkyl, —
(C═
O)N(C1-C6)alkyl, —
(CR23R24)p(C6-C12)aryl, and —
(CR23R24)p(4 to
11)-membered heterocyclyl;
any 1 or 2 carbon atoms of the (4 to
11)-membered heterocyclyl of each said R7, R8, R9, R10, R11, R12, R13, R14, R15, R16, R17, R18, R19, R20, R21, and R22 group may be optionally substituted with an oxo (═
O);
each R23 and R24 is independently selected from H and (C1-C6)alkyl;
and wherein any of the above-mentioned substituents comprising a —
CH3 (methyl), —
CH2 (methylene), or —
CH (methine) group which is not attached to a halo, —
SO or —
SO2 group or to a N, O or S atom optionally bears on said group a substituent independently selected from the group consisting of hydroxy, halo, (C1-C6)alkyl, (C1-C6)alkoxy, —
NH2, —
NH(C1-C6)(alkyl) and —
N((C1-C6)(alkyl))2;
with the proviso that —
NR2R3 is not an unsubstituted group selected from and the further proviso that when —
R1 is then —
NR2R3 is not an unsubstituted or substituted, fused or unfused group selected from or a pharmaceutically acceptable salt or solvate thereof.
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Abstract
The present invention relates to compounds with formula (I) or a pharmaceutically acceptable salt thereof:
T is a (4 to 10)-membered heterocyclyl and wherein R1, R2 and R3 are as defined in the specification. The invention also relates to pharmaceutical compositions comprising the compounds of formula (I) and methods of treating a condition that is mediated by the modulation of the 11-β-hsd-1 enzyme.
9 Citations
16 Claims
-
1. A compound of formula (I):
-
wherein;
R1 is 2-pyridinyl which is fused or substituted with 1-3 R6′
groups, with at least one R6 group being at the 6′
position of the pyridinyl;
b is 2;
R2 and R3 are taken together with the nitrogen atom to which they are attached to form a (4 to
11)-membered heterocyclyl, and the (4 to
11)-membered heterocyclyl may optionally be substituted by 1 to 3 R6 groups;
the carbon atoms of R1, R2, and R3 may each be optionally substituted by 1 to 3 R6 groups;
each R6 group is independently selected from the group consisting of halo, cyano, nitro, —
CF3, —
CHF2, —
CH2F, trifluoromethoxy, azido, hydroxy, (C1-C6)alkoxy, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, —
(CR7R8)v(C6-C12 aryl), —
(CR7R8)v(4 to
11)-membered heterocyclyl, —
(C═
O)—
R9, —
(C═
O)—
O—
R9, —
O—
(C═
O)—
R9, —
R9—
(C=O)—
O—
R10, —
(CR9R10)q(C═
O)(CR11R12)v(C6-C12)aryl, —
(CR9R10)q(C═
O)(CR11R12)v(4 to
11)-membered heterocyclyl, —
O—
(C═
O)—
NR13R14, —
NR13(C═
O)—
R14, —
(C═
O)—
NR13R14, —
R13—
(C═
O)—
NR14R15, —
NR13R14, —
NR13OR14, —
S(O)kNR13R14, —
S(O)j(C1-C6)alkyl, —
O—
SO2—
R15, —
NR15—
S(O)k—
R16, —
(CR17R18)qS(O)j(CR19R20)v(C6-C12)aryl, —
(CR17R18)qS(O)j(CR19R20)v(4 to
11)-membered heterocyclyl, —
(CR17R18)vO(CR19R20)q(C6-C12)aryl, and —
(CR17R18)vO(CR19R20)q(4 to
11)-membered heterocyclyl,-k is selected from 1 and 2;
j is selected from the group consisting of 0, 1, and 2;
t, u, p, q, and v are each independently selected from the group consisting of 0, 1, 2, 3, 4, and 5;
any 1 or 2 carbon atoms of any foregoing (4 to
11)-membered heterocyclyl groups may be optionally substituted with an oxo (═
O);
any (C1-C6)alkyl, any (C6-C12)aryl, and any (4 to
11)-membered heterocyclyl of the foregoing R6 groups may be optionally substituted with 1 to 3 substituents independently selected from the group consisting of halo, cyano, nitro, —
CF3, —
CFH2, —
CF2H, trifluoromethoxy, azido, —
OR21, —
(C═
O)—
R21, —
(C═
O)—
O—
R21, —
O—
(C═
O)—
R21, —
NR21(C═
O)—
R22, —
(C═
O)—
NR21R22, —
NR21R22, —
NR21OR22, (C1-C6)alkyl, (C2-C8)alkenyl, (C2-C6)alkynyl, —
(CR21R22)u(C6-C12)aryl, and —
(CR21R22)u(4 to
11)-membered heterocyclyl;
each R7, R8, R9, R10, R11, R12, R13, R14, R15, R16, R17, R18, R19, R20, R21, and R22 group is independently selected from the group consisting of H, (C1-C6)alkyl, —
(C═
O)N(C1-C6)alkyl, —
(CR23R24)p(C6-C12)aryl, and —
(CR23R24)p(4 to
11)-membered heterocyclyl;
any 1 or 2 carbon atoms of the (4 to
11)-membered heterocyclyl of each said R7, R8, R9, R10, R11, R12, R13, R14, R15, R16, R17, R18, R19, R20, R21, and R22 group may be optionally substituted with an oxo (═
O);
each R23 and R24 is independently selected from H and (C1-C6)alkyl;
and wherein any of the above-mentioned substituents comprising a —
CH3 (methyl), —
CH2 (methylene), or —
CH (methine) group which is not attached to a halo, —
SO or —
SO2 group or to a N, O or S atom optionally bears on said group a substituent independently selected from the group consisting of hydroxy, halo, (C1-C6)alkyl, (C1-C6)alkoxy, —
NH2, —
NH(C1-C6)(alkyl) and —
N((C1-C6)(alkyl))2;
with the proviso that —
NR2R3 is not an unsubstituted group selected fromand the further proviso that when —
R1 isthen —
NR2R3 is not an unsubstituted or substituted, fused or unfused group selected fromor a pharmaceutically acceptable salt or solvate thereof. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 11, 13)
-
-
9. A compound selected from the group consisting of:
or a pharmaceutically acceptable salt or solvate thereof.
-
10. A compound selected from the group consisting of
or a pharmaceutically acceptable salt or solvate thereof.
-
14. A compound of formula (III):
-
wherein;
R1 is pyridinyl which is fused or unfused, unsubstituted or substituted with 1-3 R6 groups;
—
(CR4R5)t(C6-C12)aryl, and —
(CR4R5)t(4 to
10)-membered heterocyclyl;
b is 2;
R2 and R3 are taken together with the nitrogen atom to which they are attached to form a (12-14)-membered heterocyclyl, and the (12-15)-membered heterocyclyl may optionally be substituted by 1 to 3 R6 groups;
each R4 and R5 is independently selected from H and (C1-C6)alkyl;
the carbon atoms of R1, R2, R3, R4, and R5 may each be optionally substituted by 1 to 3 R6 groups;
each R6 group is independently selected from the group consisting of halo, cyano, nitro, —
CF3, —
CHF2, —
CH2F, trifluoromethoxy, azido, hydroxy, (C1-C6)alkoxy, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, —
(CR7R8)v(C6-C12 aryl), —
(CR7R8)v(4 to
11)-membered heterocyclyl, —
(C═
O)—
R9, —
(C═
O)—
O—
R9, —
O—
(C═
O)—
R9, —
R9—
(C═
O)—
O—
R10, —
(CR9R10)q(C═
O)(CR11R12)v(C6-C12)aryl, —
(CR9R10)q(C═
O)(CR11R12)v(4 to
11)-membered heterocyclyl, —
O—
(C═
O)—
NR13R14, —
NR13(C═
O)—
R14, —
(C═
O)—
NR13R14, —
R13—
(C═
O)—
NR14R15, —
NR13R14, —
NR13OR14, —
S(O)kNR13R14, —
S(O)j(C1-C6)alkyl, —
O—
SO2—
R15, —
NR15—
S(O)k—
R16, —
(CR17R18)qS(O)j(CR19R21)v(C6-C12)aryl, —
(CR17R18)qS(O)j(CR19R20)v(4 to
11)-membered heterocyclyl, —
(CR17R18)vO(CR19R20)q(C6-C12)aryl, and —
(CR17R18)vO(CR19R20)q(4 to
11)-membered heterocyclyl;
k is selected from 1 and 2;
j is selected from the group consisting of 0, 1, and 2;
t, u, p, q, and v are each independently selected from the group consisting of 0, 1, 2, 3, 4, and 5;
any 1 or 2 carbon atoms of any foregoing (4 to
11)-membered heterocyclyl group may be optionally substituted with an oxo (═
O);
any (C1-C6)alkyl, any (C6-C12)aryl, and any (4 to
11)-membered heterocyclyl of the foregoing R6 groups may be optionally substituted with 1 to 3 substituents independently selected from the group consisting of halo, cyano, nitro, —
CF3, —
CFH2, —
CF2H, trifluoromethoxy, azido, —
OR21, —
(C═
O)—
R21, —
(C═
O)—
O—
R21, —
O—
(C═
O)—
R21, —
NR21(C═
O)—
R22, —
(C═
O)—
NR21R22, —
NR21R22, —
NR21OR22, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, —
(CR21R22)u(C6-C12)aryl, and —
(CR21R22)v(4 to
11)-membered heterocyclyl;
each R7, R8, R9, R10, R11, R12, R13, R14, R15, R16 , R17, R18, R19, R20, R21, and R22 group is independently selected from the group consisting of H, (C1-C6)alkyl, —
(C═
O)N(C1-C6)alkyl, —
(CR23R24)p(C6-C12)aryl, and —
(CR23R24)p(4 to
11)-membered heterocyclyl;
any 1 or 2 carbon atoms of the (4 to
11)-membered heterocyclyl of each said R7, R8, R9, R10, R11, R12, R13, R14, R15, R16, R17 , R18, R19, R20, R21, and R22 group may be optionally substituted with an oxo (═
O);
each R23 and R24 is independently selected from H and (C1-C6)alkyl;
and wherein any of the above-mentioned substituents comprising a —
CH3 (methyl), —
CH2 (methylene), or —
CH (methine) group which is not attached to a halo, —
SO or —
SO2 group or to a N, O or S atom optionally bears on said group a substituent independently selected from the group consisting of hydroxy, halo, (C1-C6)alkyl, (C1-C6)alkoxy, —
NH2, —
NH(C1-C6)(alkyl) and —
N((C1-C6)(alkyl))2;
or a pharmaceutically acceptable salt or solvate thereof. - View Dependent Claims (15)
-
-
16. A method of preparing a compound of formula (I)
wherein: -
R1 is a —
(CR4R5)t(4 to
10)-membered heterocyclyl;
b and k are each independently selected from 1 and 2;
j is selected from the group consisting of 0, 1, and 2;
t, u, p, q, and v are each independently selected from the group consisting of 0, 1, 2, 3, 4, and 5;
each R2 and R3 is independently selected from the group consisting of H, (C1-C6) alkyl, (C2-C6) alkenyl, (C2-C6) alkynyl, —
(CR4R5)t(C3-C10)cycloalkyl, —
(CR4R5)2(C6-C10)aryl, and —
(CR4R5)t(4 to
11)-membered heterocyclyl;
or R2 and R3 may optionally be taken together with the nitrogen atom to which they are attached to form a (4 to
11)-membered heterocyclyl, and the (4 to
11)-membered heterocyclyl may be optionally substituted by 1 to 3 R6 groups;
each R4 and R5 is independently selected from H and (C1-C6)alkyl;
the carbon atoms of R1, R2, R3, R4, and R5 may each be optionally substituted by 1 to 3 R6 groupseach R6 group is independently selected from the group consisting of halo, cyano, nitro, —
CF3, —
CHF2, —
CH2F, trifluoromethoxy, azido, hydroxy, (C1-C6)alkoxy, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, —
(CR7R8)v(C6-C12 aryl), —
(CR7R8)v(4 to
11)-membered heterocyclyl, —
(C═
O)—
R9, —
(C═
O)—
O—
R9, —
O—
(C═
O)—
R9, —
R9—
(C═
O)—
O—
R10, —
(CR9R10)q(C═
O)(CR11R12)v(C6-C12)aryl, —
(CR9R10)q(C═
O)(CR11R12)v(4 to
11)-membered heterocyclyl, —
O—
(C═
O)—
NR13R14, —
NR13(C═
O)—
R14, —
(C═
O)—
NR13R14, —
R13—
(C═
O)—
NR14R15, —
NR13R14, —
NR13OR14, —
S(O)kNR13R14, —
S(O)j(C1-C6)alkyl, —
O—
SO2—
R15, —
NR15—
S(O)k—
R16, —
(CR17R18)qS(O)j(CR19R20)v(C6-C12)aryl, —
(CR17R18)qS(O)j(CR19R20)(4 to
11)-membered heterocyclyl, —
(CR17R18)vO(CR19R20)q(C6-C12)aryl, and —
(CR17R18)vO(CR19R20)q(4 to
11)-membered heterocyclyl, any 1 or 2 carbon atoms of any foregoing (4 to
11)-membered heterocyclyl group may be optionally substituted with an oxo (═
O);
any (C1-C6)alkyl, any (C6-C12)aryl, and any (4 to
11)-membered heterocyclyl of the foregoing R6 groups may be optionally substituted with 1 to 3 substituents independently selected from the group consisting of halo, cyano, nitro, —
CF3, —
CFH2, —
CF2H, trifluoromethoxy, azido, —
OR21, —
(C═
O)—
R21, —
(C═
O)—
O—
R21, —
O—
(C═
O)—
R21, —
NR21(C═
O)—
R22, —
(C═
O)—
NR21R22, —
NR21R22, —
NR21OR22, (C2-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, —
(CR21R22)u(C6-C12)aryl, and —
(CR21R22)u(4 to
11)-membered heterocyclyl;
each R7, R8, R9, R10, R11, R12, R13, R14, R15, R16, R17, R18, R19, R20, R21, and R22 group is independently selected from the group consisting of H, (C1-C6)alkyl, —
(C═
O)N(C1-C6)alkyl, —
(CR23R24 )p(C6-C12)aryl, and —
(CR23R24)p(4 to
11)-membered heterocyclyl;
any 1 or 2 carbon atoms of the (4 to
11)-membered heterocyclyl of each said R7, R8, R9, R10, R11, R12, R13, R14, R15, R16, R17, R18, R19, R20, R21, and R22 group may be optionally substituted with an oxo (═
O);
each R23 and R24 is independently selected from H and (C1-C6)alkyl;
comprising steps of;
(a) treating a compound of formula (II) wherein;
R1 and b are defined as above;
with R2R3NH in the presence of a base in a solvent, wherein each R2 and R3 is defined as above.
-
Specification